Disease relevance of IGHMBP2

• Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals [1].
• Furthermore, consanguineous parents of a child with sudden infant death syndrome should be examined for IGHMBP2 mutations [2].
• The fact that we identified other, similar cases of neuropathy and early respiratory failure with and without IGHMBP2 mutations suggests genetic as well as clinical heterogeneity in these infants [3].
• Overall, there was no significant association between the IGHMBP2 variant-G allele and breast cancer risk (OR = 1.1, 95% CI = 0.9-1.3) [4].
• Smubp-2 represses the Epstein-Barr virus lytic switch promoter [5].

High impact information on IGHMBP2

• Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus [1].
• Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4) [1].
• In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13) [1].
• The serum-free conditioned medium from glial cells can quantitatively antagonize the effect of oleic acid, suggesting that glial factor activity could be due to components [lipids and/or macromolecular factors(s)] that are able to modify the properties of the neuroblastoma cell membrane [6].
• The size and specificity of this DNA-binding protein resemble GF-1, a previously described transcription factor of erythroid cells that binds to the same core motif [7].

Biological context of IGHMBP2

• Smokers carrying the IGHMBP2 variant-G allele had no significant increased breast cancer risk compared with non-smoking women with the AA genotype [4].
• Cotransfection of the recombinant GF1 expressor plasmid with JCV promoters indicates that GF1 stimulates transcription of the JCV late promoter and to a lesser extent the JCV early promoter predominantly in cells of human glial origin [8].
• Thus, GF1 is a sequence-specific DNA binding protein that may play a role in determining the glial-specific expression of JCV [8].
• Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSmuBP2 or GF1 induced apoA-I proximal promoter activity by 3-fold and that the apoA-I DRE was necessary for transactivation [9].
• A 14-bp region that partially overlaps with a 12-O-tetradecanoylphorbol-13-acetate-responsive element was required for maximal repression by Smubp-2, but some repression was also seen with a minimal promoter containing only the BZLF1 promoter TATA box and an initiation site [5].

Anatomical context of IGHMBP2

• Based on these findings we conclude that impairment of IGHMBP2 function leads to axonal degeneration, abnormal myelin formation, and motor end-plate degeneration [10].
• Overexpression of Smubp-2 in the B lymphocyte cell line BJAB caused repression of the BZLF1 gene promoter [5].
• SGF-1, a new fish cell line that is persistently infected with SnRV, was induced by inoculating SnRV into the grouper fin cell line GF-1 [11].
• Our results demonstrate that, unlike GF-1 which stimulates JCV early promoter in glial cells, overexpression of S(mu)bp-2 exhibits no drastic effect on the transcription of the viral early promoter [12].

Associations of IGHMBP2 with chemical compounds

• Relative to the Second International hCG standard (MRC 61/6) GF-1 had an immunological potency of 21 000 i.u./mg as measured in a specific hCG-beta radioimmunoassay and, using the ovarian ascorbic acid depletion assay, an apparent biological potency of 24 064 i.u./mg [13].
• In the present study, all patients were on warfarin therapy for at least six weeks, and the ATF equation was modified by multiplying it by the prothrombin ratio (PR) to give a corrected ATF (CATF) [14].

Physical interactions of IGHMBP2

• We report here an additional significant association between IgA nephropathy and an SNP located in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2) at chromosome 11q13.2-q13 [15].

Analytical, diagnostic and therapeutic context of IGHMBP2

• In both patients, we identified genomic rearrangements of the other allele of IGHMBP2 by means of Southern blotting [16].
• Using 1067 cases and 1110 controls from a population-based case-control study, we sought to clarify the potential role of the IGHMBP2 Thr671Ala polymorphism (A to G substitution) alone and as a modifier of the effects for cigarette smoking and PAH-DNA adducts on breast cancer risk [4].
• However, when GF-1 cells were used for titration, the titre of the culture supernatant from GNNV-infected SGF-1 cells was much higher than that from GNNV-infected GF-1 cells [11].
• This CATF was then further modified to achieve agreement with the INR by adjusting the linear regression line by means of analytic geometry, so that the CATF-INR regression line now had a slope of one and passed through the origin [14].

References